Disubstituted malonic ester and process of preparing the same



Patented July 25, 1944 DISUBSTITUTED MALONIC ESTER AND PROCESS OF PREPARING THE SAME Lewis A. Walter and Louis 11. Goodson, East Orange, N. J., assignors to The Maltbie Chemical Company, Newark, N. 1., a corporation of New Jersey No Drawing, Application May 6, 1942,

; Serial No. 441,972

25Clalms.

The present invention relates to certain new and useful compositions of matter, namely disubstituted malonic esters having the formula:

o 1 wherein R, R, and R" are hydrocarbon groups, either saturated or unsaturated, and either the same or diil'erent, and each containing not more than six carbon atoms, and wherein the sum of the carbon atoms in R,,R' and R." does not exceed l; and wherein R has a carbon atom directly attached to the sulfur atom of the thiocarbinyl group compounds of that class having useful sedative and hypnotic properties.

Our new malonic esters may be prepared by condensing an a-(ll'llOl'O sulfide, of the type R" R s cri-ci (in which R and R." have the significance stated above) with a sodium malonic ester of the type:

scribed by way of illustration are colorless or slightly tinted liquids.

Exams: 1 n -Butylthioethylidene ethyl malonic ester CH: CH CH CH CHPS7 053 COOChHs To 0.3 mole of metallic sodium dissolved in 150 cc. absolute alcohol is added 0.3 mole of ethyl malonic ester. The alcohol is removed in a vacuum, 200 cc. dry toluene is added, and the mixture is stirred and cooled to 0' to 5 C. during the dropwise addition of 0.31 mole of n-butyl-(a-chloroethyl) sulfide. After standing over night at room temperature, the mixture is warmed on a water bath until it no longer gives a basic test with moist litmus. The toluene solution is then washed with water and fractionally distilled to give n-butylthioethylidene ethyl malonic ester, boiling at approximately 116-117 at a pressure COOCIHI 5 of 0.6 mm. of mercury to yield).

(in which R and R'" have the significance stated I above), in the presence of an organic solvent such as toluene, and under appropriate conditions of temperature, such as those which are hereafter fully described and illustrated in the examples Exsmmr: 2

Ethylthioisobutylidene ethyl malonic ester One mole of ethyl mercaptan is chilled to 10 C. and vigorously stirred while one mole of isobutyraldehyde is added drop by drop over a period of 2 to 3 hours. At the same time, a stream of hydrogen chloride is passed into the mixture and the temperature is kept below 0 C. by external cooling. When addition of the aldehyde is complete, and hydrogen chloride is no longer rapidly absorbed, the aqueous layer is separated and the oily layer is dried at 0 C. with 25-30 grams of anhydrous calcium chloride. The calcium chloride is then filtered off and the product is aerated under reduced pressure to remove hydrogen chloride. It is then added immediately to a solution of 0.6 mole' of sodioethyl malonic ester in 300 cc. of toluene at a temperature not exceeding 5 C. The mixture is stirred until the reaction is complete; then the toluene solution is washed with 'water and distilled to give ethylthioisobutylidene ethyl malonic ester, which boils at approximately ,112" at a pressure of 1.2 mm. of mercury.

lloprmlthiopropvlideu ethyl malonic ester 1 on. n can CA. eoocm.

One mole of isopropyl mercaptan is chilled to c. and is vigorously stirred while one mole of n-propionaldehyde is added drop by drop over aperiod oi about2to8hours. Atthe same time, a stream of hydrogen chloride is passed into the mixture and the temperature is kept below 0 C. by external cooling. When addition of the aide-- hyde is complete, and hydrogen chloride is no longer rapidly absorbed. the aqueous layer is separated and the oily layer is dried at 0 C. with -80 grams oi anhydrous calcium chloride. The calciumchloride is removed by filtration, and the product is aerated under reduced pressure to remore hydrogen chloride. It is then added im- 0. when hydrogen chloride is no longer rapidly absorbed. the queous layer is separated and the product is dried with 20-30 grams oi calcium chloride at 0' C. The calcium chloride is removed by filtration: the product is aerated under reduced pressure to remove hydrogen chloride, and is then added immediately to a solution 01' one mole of sodioisobutyl malonic ester in 500 cc. oi. toluene, while maintaining the temperature below 5' C. The mixture is then stirred until the reaction is complete; then the toluene solution is washed with water and tractionally distilled to give the desired ester, which has a boiling point of approximately 110-112 at a pressure of 1 mm. gt mercury, and with a yield of about 60% to The following disubstituted malonic esters, which we have prepared, including the examples given above, are embodiments of our invention, and are illustrative of the generic class of compounds described and claimed herein, it being understood, however, that the generic class of compounds is not limited to the ethyl esters, but includes esters in which R is a lower alkyl medlately to a solution of 0.0 mole of sodioethyl group.

Malonic acid wherein:

Pressure Aplproximate bo ing polnt COOCJI malonic ester in 300 cc. toluene at a temperature not exceeding 5' C. The mixture is stirred until the reaction is complete; then thetoluene solution is washed with water and distilled to give the desired ester, which has a boiling point of approximately 104-106 C. at a pressure 01' 1.2 mm. of mercury. The yield, based on mercaptan, is about 25% to Euros: 4 lillulthioethylidene isobutvl malonic ester 11 on. cHFc-cm-s-o coocim n-cm coocm.

OKs-C A mixture of one mole of allyl mercaptan and 0.83 mole of paraldehyde is chilled to 10 C. and is then rapidly stirred while a stream of hydrogen chloride is passed into the mixture at such a rate that the temperature does not rise abo e 0 served, according to a In the foregoing examples, the boiling points are approximate, and at about the pressures given; but are boiling points which we actually obprocedure believed to be reliable.

Procedures suitable for making a-ChlOlOSlllfidCS suitable for use as starting materials in the preparation of disubstituted malonic esters according to this application (e. g. a-chloroethyl sulfides) are disclosed in our co-pending application Serial No. 441,971, filed May 6, 1942, for a-Chloroethyl sulfides and process oi preparing the same. Other such procedures are disclosed in Examples 2, 3 and 4 above.

The examples given above, and illustrative processes for their production, include the best embodiments of our present invention now known to us: but it 'is to be understood that the invention is not necessarily or specifically limited thereto, and may, under proper circumstances, have other embodiments, produced in other ways, without departure from the spirit of the invention, and within the scope oi. the following claims.

We claim: 1. As a new and useful chemical compound, a disubstituted malonic ester having the Iormula:

wherein R, R and R" are hydrocarbon groups each of which contains not more than six carbon atoms. and wherein the sum of the carbon atoms in R, R and R" does not exceed and wherein R has a carbon atom directly attached to the sulfur' atom of the thiocarbinyl group; and wherein each R'" is a lower alkyl group.

2. A disubstituted malonic ester according to claim 1 wherein R, R and R are all saturated groups.

3. A. disubstituted malonic ester according to claim 1 wherein R, R and R" are primary hydrocarbon groups.

4. A disubstituted malonic ester according to claim 1 wherein R, R and R" are all primary, saturated hydrocarbon groups.

5. A .disubstituted malonic ester according to claim 1 wherein R and R are primary hydrocarbon groups and R" is a methyl group.

6. A disubstituted malonic ester according to claim 1 wherein R and R are both primary, saturated hydrocarbon groups and R" is a methyl group.

7. A disubstituted malonic ester according to claim 1 wherein R is a primary, saturated hydrocarbon group containing Iour carbon atoms, R is a primary hydrocarbon group, and R" is a methyl group.

8. A disubstituted malonic ester according to claim 1 wherein R is a primary, saturated hydrocarbon group containing four carbon atoms, R.

is a primary, saturated hydrocarbon group, and 40 R" is a methyl group.

9. A disubstituted malonic ester according to claim 1 wherein R is a primary hydrocarbon group, R is an ethyl group, and R" is a methyl group.

10. A disubstituted malonic ester according to claim 1 wherein R is a primary, saturated hydrocarbon group. R is an ethyl group, and R" is a methyl group.

11. A disubstituted malonic ester according to claim 1 wherein R is a primary, saturatemhydrocarbon group containing four carbon atoms, R

is an ethylgroup, and R is a methyl group.

12. A disubstituted malonic ester according to claim 1 wherein R is a secondary hydrocarbon group, and R and R" are primary hydrocarbon p 3. A disubstituted malonic ester according to claim 1' wherein R is a secondary hydrocarbon group, and R andR" are both primary, saturated hydrocarbon groups.

14. A disubstituted malonic ester according to claim 1 wherein R is a secondary hydrocarbon group, R is a saturated, primary hydrocarbon group. and R" is a methyl group.

15. A disubstituted malonic ester according to claim 1 wherein R is a saturated, secondary hydrocarbon group, R is a saturated, primary hydrocarbon group, and R." is a methyl group.

16. A disubstituted malonic ester according to claim 1 wherein R and R are both primary hys drocarbon groups, and R is a secondary hydrocarbon group. 17. A disubstituted malonic ester according to claim 1 wherein R and R are both saturated, primary hydrocarbon groups and R" is a secondary hydrocarbon group.

18. A disubstituted malonic ester according to claim 1 wherein R is an ethyl group, R is a primary hydrocarbon group and R" is a secondary hydrocarbon group.

19. A disubstituted malonic ester according to claim 1 wherein R is an ethyl group, R is a saturated, primary hydrocarbon group, and R" is a secondary hydrocarbon group.

20. A disubstituted malonic ester according to claim 1 wherein R is an ethyl group, R is a saturated, primary hydrocarbon group and R is an isopropyl group.

21. A disubstituted malonic ester according to claim 1 wherein R and R are both ethyl groups and R" is a secondary hydrocarbon group.

22. n-Butylthioethylidene ethyl malonic ester, having the formula:

80 /CO 0 Grill C CHrCH; CO 00,3;

OH: H CH:

S CHz H C cmcrncni \COOCIHI 24. Ethylthioisobutylidene ethyl malonic ester, having the formula:

H 5 CHg--CHI cmcm-s- 000cm,

omen. 0000.11. 25. The process of producing a disubstituted malonic ester according to claim 1, which comprises treating approximately one mole 01! an achlorosulflde or the type:

I R V R-s-b-c:

with a sodio malonic ester or the type:

LEWIS A. WAL'IER. LOUIS H. GOODSON.

. CERTIFICATE OF CORRECTIO NA Patent No. 2 9 254 H "July 2 191m.

was A. mnma, n-.l' L, It is hereby certified thaterror eppears hijhe printed specification of the-above numhered patent requiring correction as follows": Paigefz line 28, 1n the table, for the worde "Halonio acid read "Yelena eater-* 1 page 5, first column, line 17, claim 2 fox R and-R" read u- R' and R"---; and that-the said ,Lettere Patent should be-read with this coxfi'ec tion therein that the same may conform to the record of the case iziish'e Patent Office. v. w and sealed this 1mm day of November, A. 1). 191m.

" Leslie Frazer (Seal) Acting. Cdnuniiiioher of Patents} 

